Brucella spp. is the causative agent of brucellosis, an extremely important disease worldwide. Innate immune cells detect pathogens via repeated cellular patterns (PAMPs) such as the Brucella suis (B. suis) lipopolysaccharide (LPS) coat on Gram-negative bacteria, which act as an important virulence factor of Brucella. B.suis LPS may be an issue for pro-inflammatory cytokine induction such as interleukin-1 (IL-1), interleukin-18 (IL-18) and interleukin-1â (IL-1â), which released from immune cells to mediate downstream inflammatory effects. To elucidate the mechanism of how B.suis LPS affects the secretion of IL-1, IL-18 and IL-1â in macrophages. We identified the up-regulation of caspase-11 in a porcine alveolar macrophages (PAM) cells stimulated with B.suis LPS. Furthermore, specific small interfering RNA (siRNA) targeting caspase-11 effectively inhibited B.suis LPS stimulated IL-1, IL-18 and IL-1â release from PAM. The results indicated that the concentrations of IL-1, IL-18 and IL-1â of caspase-11 siRNA pretreated group were lower than that of control significantly. Caspase-11 plays an important role in IL-1, IL-18 and IL-1â secretion from porcine alveolar macrophage cells stimulated with Brucella suis LPS, and these findings might aid our understanding of the pathogenic mechanisms of Brucella and provide an entirely new innate immune response mechanism underlying macrophages dysfunction during Brucella infection.